Tracking Changes in SARS-CoV-2 Spike: Evidence that D614G Increases Infectivity of the COVID-19 Virus

被引:2700
作者
Korber, Bette [1 ,2 ]
Fischer, Will M. [1 ]
Gnanakaran, Sandrasegaram [1 ]
Yoon, Hyejin [1 ]
Theiler, James [1 ]
Abfalterer, Werner [1 ]
Hengartner, Nick [1 ]
Giorgi, Elena E. [1 ]
Bhattacharya, Tanmoy [1 ]
Foley, Brian [1 ]
Hastie, Kathryn M. [3 ]
Parker, Matthew D. [4 ,5 ]
Partridge, David G. [6 ]
Evans, Cariad M. [6 ]
Freeman, Timothy M. [4 ,5 ]
de Silva, Thushan, I [6 ,7 ]
McDanal, Charlene [8 ,9 ]
Perez, Lautaro G. [8 ,9 ]
Tang, Haili [8 ,9 ]
Moon-Walker, Alex [3 ,10 ,11 ]
Whelan, Sean P. [11 ]
LaBranche, Celia C. [8 ,9 ]
Saphire, Erica O. [3 ]
Montefiori, David C. [8 ,9 ]
机构
[1] Los Alamos Natl Lab, Theoret Biol & Biophys, Los Alamos, NM 87545 USA
[2] New Mexico Consortium, Los Alamos, NM 87545 USA
[3] La Jolla Inst Immunol, La Jolla, CA 92037 USA
[4] Univ Sheffield, Sheffield Biomed Res Ctr, Sheffield S10 2HQ, S Yorkshire, England
[5] Univ Sheffield, Sheffield Bioinformat Core, Sheffield S10 2HQ, S Yorkshire, England
[6] Sheffield Teaching Hosp NHS Fdn Trust, Sheffield S10 2JF, S Yorkshire, England
[7] Univ Sheffield, Med Sch, Dept Infect Immun & Cardiovasc Dis, Sheffield S10 2RX, S Yorkshire, England
[8] Duke Human Vaccine Inst, Durham, NC 27710 USA
[9] Dept Surg, Durham, NC 27710 USA
[10] Harvard Univ, Program Virol, Boston, MA 02115 USA
[11] Washington Univ, Dept Mol Microbiol, St Louis, MO 63130 USA
基金
英国惠康基金; 英国医学研究理事会;
关键词
RESPIRATORY SYNDROME CORONAVIRUS; NEUTRALIZING ANTIBODY-RESPONSE; SARS CORONAVIRUS; CELL ENTRY; EVOLUTION; MECHANISMS; EMERGENCE; INSIGHTS; EPIDEMIC; DISEASE;
D O I
10.1016/j.cell.2020.06.043
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
A SARS-CoV-2 variant carrying the Spike protein amino acid change D614G has become the most prevalent form in the global pandemic. Dynamic tracking of variant frequencies revealed a recurrent pattern of G614 increase at multiple geographic levels: national, regional, and municipal. The shift occurred even in local epidemics where the original D614 form was well established prior to introduction of the G614 variant. The consistency of this pattern was highly statistically significant, suggesting that the G614 variant may have a fitness advantage. We found that the G614 variant grows to a higher titer as pseudotyped virions. In infected individuals, G614 is associated with lower RT-PCR cycle thresholds, suggestive of higher upper respiratory tract viral loads, but not with increased disease severity. These findings illuminate changes important for a mechanistic understanding of the virus and support continuing surveillance of Spike mutations to aid with development of immunological interventions.
引用
收藏
页码:812 / +
页数:35
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